Wilson disease

Wilson disease is an inherited disorder that causes excess copper buildup in the liver. In this disease, copper accumulates in various body tissues until it causes damage to multiple organ systems, including the liver tissue, the central nervous system, and more.

Although effective treatment for this disease is available, without early diagnosis and therapy, irreversable damage may occur to the brain, the liver, and other organs and tissues. The prevalence of this disease is 1 in 30,000, symptoms usually begin to develop before age forty. However, several cases have been documented in which the disease was diagnosed in children, or in older people, although these cases are especially rare.


What is the pathophysiology of the disease?

Wilson’s disease is caused by a deficiency in the protein ATP7B, which prevents it from binding to copper. Normally, copper is derived exclusively from food, is bound to the protein albumin, and makes its way to the liver, where it is bound to a protein called ceruloplasmin. Assisted by the protein ATP7B, it is released into the blood and excreted from the body, mainly via feces.

When the protein ATP7B is deficient, copper cannot be removed from the body and instead begins to accumulate in different tissues.



The main impact of excess copper accumulation is damage to the liver and the central nervous system. Damage to the central nervous system appears after the liver becomes damaged and indicates that the liver is completely saturated with copper.

Among the various symptoms in the liver:

  • Liver dysfunction that can only be detected through laboratory testing, without apparent external signs.
  • Symptoms resembling viral hepatitis.
  • Symptoms resembling chronic liver disease.
  • An acute inflammation of the liver manifested in encephalopathy, ascites, and jaundice.
  • Cirrhosis of the liver.


Symptoms in the central nervous system:

In most cases, no neurological manifestation will occur before ten years of age, but if this damage does appear, it will usually manifest as dystonia.

Without appropriate treatment, neurological damage will manifest during a patient’s twenties, and include various movement disorders such as uncontrolled limb tremors, involuntary movements, and muscle cramps and spasms. In addition, swallowing difficulties, speech difficulties, and headaches may occur.

Around twenty percent of patients suffer from psychiatric symptoms, manifesting as schizophrenia, various phobias, depression, bipolar disorder, and irregular behavior.


What other organ systems can the disease affect?

  • Copper deposition in the cornea, which does not affect vision, appears in 98 percent of patients suffering from neurological damage, and 80 percent of all patients. This phenomenon is known as Kayser–Fleischer rings.
  • Hormone disturbances, such as amenorrhea, hypothyroidism, testicular atrophy.
  • Heart dysfunction such as cardiomyopathy, heart failure, arrhythmia, and more.
  • Kidney damage occurs among a fifth of patients.
  • Splenomegaly (enlargement of the spleen) and hemolytic anemia due to liver cirrhosis.


Diagnosis – can the disease be diagnosed prenatally?

The mutation to the gene ATP7B, located on chromosome 13, has an autosomal recessive inheritance pattern. Since there are over 300 different gene mutations that can cause the disease, genetic screening tests and carrier screening are not typically offered to the public.

Accordingly, most cases of Wilson’s disease are diagnosed based on typical symptoms. A final diagnosis is given through testing ceruloplasmin levels in the blood (ceruloplasmin levels are usually low in people with Wilson disease), urine copper tests (require 24-hour collecting), testing the levels of copper in the blood and liver, and more.

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